The primary aim of the study is to assess the genotype - phenotype correlations of the CNS manifestations of late infantile neuronal ceroid lipofuscinosis (LINCL), a fatal, rare, recessive disorder of the CNS in children. This study will be accomplished by comparing the genotype to a neurologic assessment and Weill Cornell LINCL scale, the UBDRS scale, the standardized CHQ quality of life scale, and the Mullen scale; magnetic resonance imaging (MRI); and routine clinical evaluations. This study is designed to run parallel to a separate study which is being done by the Department of Genetic Medicine, which will use gene transfer to treat the central nervous system (CNS) manifestations of late infantile neuronal ceroid lipofuscinosis.

Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:

Direct CNS Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human CLN2 cDNA to Children with Late Infantile Neuronal Ceroid Lipofuscinosis [ Time Frame: The patient will be monitored in intervals within 18 months after the gene has been injected. ] [ Designated as safety issue: Yes ]

The purpose of this Phase I study is to test the safety of AAVrh.10CUhCLN2 and see what effects (good and bad) it has as it relates to your child's condition and if it is a safe and effective treatment for Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL).

Biospecimen Retention: Samples With DNA

whole blood, serum

Estimated Enrollment:

32

Study Start Date:

March 2010

Estimated Study Completion Date:

April 2025

Estimated Primary Completion Date:

April 2020 (Final data collection date for primary outcome measure)

Detailed Description:

This protocol is designed to study the natural disease process of LINCL. We propose to assess the correlation between genotype (genetic constitution) and phenotype (observable characteristics) of late infantile neuronal ceroid lipofuscinosis (LINCL) in children diagnosed with LINCL in all stages. LINCL is a form of Batten disease that affects the brain of children and prevents it from functioning properly. These children are born with genetic changes called mutations that result in the inability of the brain to properly recycle proteins in the brain. The recycling failure leads to death of the nerve cells in the brain and progressive loss of brain function. Children with Batten disease are normal at birth but by age 2 to 4 have motor and vision problems which progress rapidly to death at age approximately 10 years old. There are no therapies available to treat the disease. This study is designed to run parallel to the gene transfer protocol, which will include 16 individuals in two groups: Group A will receive 9.0x10^11 genome copies (gc) of the vector and Group B will receive 2.85x10^11 gc; we anticipate that we will be able to capture a one-time genotype - phenotype snapshot for all n=32, and an 18 months genotype - phenotype progression assessment for n=16.

Eligibility

Ages Eligible for Study:

2 Years to 18 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Sampling Method:

Probability Sample

Study Population

The study will be carried out in children diagnosed with LINCL in all stages.

Criteria

Inclusion Criteria.

Definitive diagnosis of LINCL, based on clinical phenotype and genotype.

The subject must be between the age of 2 and 18 years.

The subject will not previously have participated in a gene transfer or stem cell study.

Parents of study participants must agree to comply in good faith with the conditions of the study, including attending all of the required baseline and follow-up assessments, and both parents or legal guardians must give consent for their child's participation.

Exclusion criteria.

Presence of other significant medical or neurological conditions may disqualify the subject from participation in this study e.g.,malignancy, congenital heart disease, liver or renal failure.

Subjects without adequate control of seizures.

Subjects with heart disease that would be a risk for anesthesia or a history of major risk factors for hemorrhage.

Subjects who cannot participate in MRI studies.

Concurrent participation in any other FDA approved Investigational New Drug.

Subjects with history of prolonged bleeding or abnormal platelet function or taking aspirin.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01035424